Patients included in the study with high risk acute myeloid leukemia or myelodysplastic syndrome as defined will receive an allogeneic transplantation conditioned by either myeloablative or reduced regimen. Following allogeneic transplantation, patients will receive a maintenance regimen combining chemotherapy with azacitidine (aza) and immunotherapy with donor lymphocyte infusion.

An A'Hern procedure will be used (cf. 11.1): If the number of patients not relapsed at two year will be 18 or more out of 24 patients, the null hypothesis will be rejected and the relapse rate will be considered acceptable.

Secondary Outcome Measures:

Evaluation of disease-free survival (DFS) at 2 years from transplantation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

cumulative incidence function for disease free survival at 2 years from transplantation, GVHD, death from leukaemia and non-relapse mortality will be estimated (patients are at risk not only for relapse but can also be "removed" from possible relapse because of competing events such as death in remission (due to infection or GVHD)).

To evaluate toxicity induced by the azacitidine and DLI, different parameters will be studied:Cell Blood Count with differential, liver function tests, serum creatinine, BUN and total protein will be performed weekly from the time of initiation of azacitidine administration until completion of the last DLI. Performance Status,Acute GVHD,Bone marrow aspiration with evaluation of morphological response as well as chimerism from peripheral blood will be performed prior starting azacitidine, following 3 cycles of azacitidine and after the seventh cycle and twelfth cycle of azacitidine.

Azacitidine (AZA) is to be administered every 28 days beginning day +56 to 100 posttransplant for one year provided the patients has a platelet count of >15 x 109/L without transfusion for at least 2 successive days, and an absolute neutrophil count of >1 x 109/L without growth factor for at least 2 successive days, and no acute GVHD greater than grade I and no clinical evidence of life-threatening infection. AZA is given 32 mg /m²/day subcutaneously for 5 days every 28 days (

Other: DLI

Donor lymphocyte infusion (DLI) is to be given from day +126 (week 18) in patients without immunosuppressive therapy for at least one month and following 3 cycles of AZA, and without clinical signs of GVHD, and without uncontrolled infection and without a recent history of >grade 2 acute GVHD. DLI are schedules every 8 weeks. There are 3 DLI scheduled.

If first cycle of AZA is postponed beyond day 56 (maximum to Day 100), all subsequent cycles and DLI will be post poned too.

Eligibility

Ages Eligible for Study:

18 Years to 70 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients with high risk acute myeloid leukemia undergoing allogeneic transplantation with either a familial or an unrelated donor.

Or Patients with high risk myelodysplastic syndrome undergoing allogeneic transplantation with either a familial or an unrelated donor.

High risk MDS is defined as :

MDS with intermediate-2 group and higher risk group according to IPSS criteria

Age 18 - 70 years.

Availability of an HLA identical family donor or unrelated donor with matching in 10/10 alleles (HLA-A, B, C, DRB1, DQB1) or maximum of 1 allele or antigen mismatch OR family donor with maximum 1 allele mismatch.

Conditioning regimen to allogeneic transplantation may be either myeloablative or reduced.

Be able to understand and sign informed consent.

Affiliation number to National Health Care System

Men and women of childbearing potential must use effective contraception during and up to 3 months after treatment.

Exclusion Criteria:

The presence of any one exclusion criteria renders the patient ineligible:

Patient in full relapse post-transplant (>20% blasts in the bone marrow) following allogeneic transplant

Acute GVHD grade II-III. Patient with grade I GVHD may be included (see annex 1 for GHVD grade definition).

Active uncontrolled infection.

Denied informed consent.

Treatment with other investigational drugs following allogeneic transplantation.

No effective contraception

Lactating females

Pregnant woman

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01541280